Impact of Nano- and Micro-Sized Chromium(III) Particles on Cytotoxicity and Gene Expression Profiles Related to Genomic Stability in Human Keratinocytes and Alveolar Epithelial Cells

Paul Schumacher; Franziska Fischer; Joachim Sann; Dirk Walter; Andrea Hartwig

doi:10.3390/nano12081294

Impact of Nano- and Micro-Sized Chromium(III) Particles on Cytotoxicity and Gene Expression Profiles Related to Genomic Stability in Human Keratinocytes and Alveolar Epithelial Cells

Nanomaterials (Basel). 2022 Apr 11;12(8):1294. doi: 10.3390/nano12081294.

Authors

Paul Schumacher¹, Franziska Fischer¹, Joachim Sann^{2

3}, Dirk Walter^{4

5}, Andrea Hartwig¹

Affiliations

¹ Department of Food Chemistry and Toxicology, Institute of Applied Biosciences (IAB), Karlsruhe Institute of Technology (KIT), Adenauerring 20a, 76131 Karlsruhe, Germany.
² Institute of Physical Chemistry, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.
³ Center for Materials Research (LaMa/ZfM), Justus-Liebig-University Giessen, Heinrich-Buff-Ring 16, 35392 Giessen, Germany.
⁴ Laboratories of Chemistry and Physics, Institute of Occupational and Social Medicine, Justus-Liebig-University Giessen, Aulweg 129, 35392 Giessen, Germany.
⁵ Institute of Inorganic and Analytical Chemistry, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.

Abstract

Exposure to Cr(VI) compounds has been consistently associated with genotoxicity and carcinogenicity, whereas Cr(III) is far less toxic, due to its poor cellular uptake. However, contradictory results have been published in relation to particulate Cr₂O₃. The aim of the present study was to investigate whether Cr(III) particles exerted properties comparable to water soluble Cr(III) or to Cr(VI), including two nano-sized and one micro-sized particles. The morphology and size distribution were determined by TEM, while the oxidation state was analyzed by XPS. Chromium release was quantified via AAS, and colorimetrically differentiated between Cr(VI) and Cr(III). Furthermore, the toxicological fingerprints of the Cr₂O₃ particles were established using high-throughput RT-qPCR and then compared to water-soluble Cr(VI) and Cr(III) in A549 and HaCaT cells. Regarding the Cr₂O₃ particles, two out of three exerted only minor or no toxicity, and the gene expression profiles were comparable to Cr(III). However, one particle under investigation released considerable amounts of Cr(VI), and also resembled the toxicity profiles of Cr(VI); this was also evident in the altered gene expression related to DNA damage signaling, oxidative stress response, inflammation, and cell death pathways. Even though the highest toxicity was found in the case of the smallest particle, size did not appear to be the decisive parameter, but rather the purity of the Cr(III) particles with respect to Cr(VI) content.

Keywords: Cr(VI) release; Cr2O3 particles; DNA damage signaling; DNA repair proteins; cell death pathways; cytotoxicity; gene expression profiles; oxidative stress.